Ischemic preconditioning and superoxide dismutase protect against endothelial dysfunction and endothelium glycocalyx disruption in the postischemic guinea-pig hearts
Ischemic preconditioning and superoxide dismutase protect against endothelial dysfunction and endothelium glycocalyx disruption in the postischemic guinea-pig hearts
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DOI：
10.1023/a:1006867214448
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发表时间：
1998-09-01
影响因子：
4.3
通讯作者：
Maczewski, M
中科院分区：
文献类型：
--
作者：
Beresewicz, A;Czarnowska, E;Maczewski, M
本文观察了缺血预处理和超氧化物歧化酶（SOD）对离体豚鼠心脏缺血后内皮糖萼和内皮依赖性舒张功能的影响。实验分为7组：1组为假有氧灌注组，2组为缺血40 min再灌注组，3组为缺血40 min再灌注组，4组为缺血5 min再灌注（IPC）组，4组为缺血40 min再灌注前IPC组，5组为缺血40 min再灌注后IPC组。第5组在标准缺血/再灌注前进行IPC，第6组在标准缺血/再灌注后进行SOD灌注（150 U/ml）在缺血40 min前5 min开始，并在再灌注期的最初5 min持续;第7组用NO合酶抑制剂L-NAME有氧灌注80 min，以产生与缺血/再灌注无关的内皮功能障碍模型。冠状动脉血流对乙酰胆碱（ACh）和硝普钠（SNP）的反应分别被用作内皮依赖性和内皮非依赖性血管功能的测量。一氧化氮合酶抑制剂L-NAME引起的冠状动脉血流减少可作为基础内皮依赖性血管舒张功能的测量指标。完成每个实验方案后，用钌红或氯化镧对心脏进行染色，以进行内皮糖萼的电子显微镜评价。虽然缺血仅导致糖萼出现轻微的絮状外观，但在缺血/再灌注心脏中，糖萼被破坏，这表明再灌注损伤导致了糖萼损伤。此外，缺血/再灌注心脏对ACh和L-NAME的冠状动脉血流反应受损，而对SNP的反应无变化。IPC可防止糖萼的破坏以及ACh和L-NAME反应的恶化。此外，SOD还能防止糖萼的改变和ACh反应的损害。L-NAME有氧灌注80 min后，心脏的糖萼似乎没有变化。最后：（1）缺血后豚鼠心脏内皮依赖性冠状动脉舒张功能的损害可被内皮糖萼破坏所抵消;（2）这两种变化均被SOD所阻止，提示自由基在其发生机制中的作用;（3）这两种变化均被IPC所阻止。因此，我们推测，糖萼的改变有助于缺血后心脏内皮功能障碍的机制。
The effect of ischemic preconditioning and superoxide dismutase (SOD) on endothelial glycocalyx and endothelium-dependent vasodilation in the postischemic isolated guinea-pig hearts was examined. Seven groups of hearts were used: group 1 underwent sham aerobic perfusion; group 2 was subjected to 40 min global ischemia without reperfusion; group 3, 40 min ischemia followed by 40 min reperfusion; group 4 was preconditioned with three cycles of 5 min global ischemia followed by 5 min of reperfusion (IPC), prior to 40 min ischemia; group 5 was subjected to IPC prior to standard ischemia/ reperfusion; group 6 underwent standard ischemia/reperfusion and SOD infusion (150 U/ml) was begun 5 min before 40 min ischemia and continued during the initial 5 min of the reperfusion period; group 7 was subjected to 80 min aerobic perfusion with NO-synthase inhibitor, L-NAME, to produce a model of endothelial dysfunction independent from the ischemia/reperfusion. Coronary flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were used as measures of endothelium-dependent and endothelium-independent vascular function, respectively. Reduction in coronary flow caused by NO-synthase inhibitor, L-NAME, served as a measure of a basal endothelium-dependent vasodilator tone. After completion of each experimental protocol, the hearts were stained with ruthenium red or lanthanum chloride for electron microscopy evaluation of the endothelial glycocalyx. While ischemia led only to a slightly flocculent appearance of the glycocalyx, in ischemia/reperfused hearts the glycocalyx was disrupted, suggesting that it is the reperfusion injury which leads to the glycocalyx injury. Moreover, the coronary flow responses to ACh and L-NAME were impaired, while the responses to SNP were unchanged in the ischemia/reperfused hearts. The disruption of the glycocalyx and the deterioration of ACh and L-NAME responses was prevented by IPC. In addition, the alterations in the glycocalyx and the impairment of ACh responses were prevented by SOD. The glycocalyx appeared to be not changed in the hearts subjected to 80 min aerobic perfusion with L-NAME. In conclusion: (1) the impairment of the endothelium-dependent coronary vasodilation is paralleled by the endothelial glycocalyx disruption in the postischemic guinea-pig hearts; (2) both these changes are prevented by SOD, suggesting the role of free radicals in the mechanism of their development; (3) both changes are prevented by IPC. We hypothesize, therefore, that alterations in the glycocalyx contribute to the mechanism of the endothelial dysfunction in the postischemic hearts.